Abstract 257: Mapping of Chromosome 2 Regions Linked to Vascular Inflammation using Congenic Rats
Background: Chromosome 2 introgression from normotensive Brown Norway rats (BN) into hypertensive Dahl salt sensitive (SS) background (consomic SB2) reduced vascular inflammation and restored Treg function. We hypothesized that the BN chromosome 2 contains genes that reduce vascular inflammation, which could be mapped using congenic rats containing different portions of BN chromosome 2 on the SS background.
Methods: Twelve-to-13 week old male BN, SS, SB2, congenic (SB)A,
SBB and SBE rats fed normal salt diet were studied. Systolic blood pressure (SBP) was measured by telemetry. Aortic vascular cell adhesion molecule 1 (VCAM-1) and fibronectin expression, collagen content and reactive oxygen species (ROS) production were determined. Spleen Treg (CD4+CD25hi) and CD4+CD25- T lymphocytes were characterized and cultured. Transforming growth factor (TGF)-β, tumor necrosis factor (TNF)-α, interleukin (IL)-10, IL-17 and IL-6 were measured in culture media.
Results: SS, SB2 and SBE exhibited 20 mmHg higher SBP compared
to BN, SBA, and SBB (P<0.05). Aortic and perivascular ROS production and aortic VCAM-1 expression were ≥2.7- and ~1.5-fold greater, respectively, in SS and SBB (P<0.05) compared to BN, SB2, SBA and SBE. Aortic media collagen content was 3-fold greater in SS and 1.7-fold in SB2 and SBB (P<0.05) compared to BN, SBA and SBE. Aortic fibronectin expression was ~1.5-fold higher in SS and SBE (P<0.05) compared to SB2 and SBA or BN. The percentage of spleen CD4+CD25- cells was higher in SS, SB2 and SBE (~16%) compared to BN, SBA and SBB (~12%, <0.05). Treg percentage was lower in SBA (2%) compared to SS and SB2 (3%, P<0.05). CD4+CD25- from SS or SBB secreted less TNF-α, IFN-γ and IL-6 (≤141, 1428 and 13 pg/105 cells, respectively, P<0.05), compared to SB2 and SBE (~320, 2350 and 50 pg/105 cells, respectively) or BN (458, 3552 and 57 pg/105 cells, respectively). Treg IL-10 and IL-17 production was higher in SB2 (9597 pg/105 cells), and SS and SB2 (>90 pg/105 cells), respectively (P<0.05), compared to congenic rats (~2540 and 23 pg/105 cells, respectively) or BN (2497 and 9 pg/105 cells).
Conclusion: Some genes regulating vascular injury and inflammatory responses are contained within the fragment of BN-chromosome 2 present in congenic SBA and SBE rats.
- © 2013 by American Heart Association, Inc.